It is well known that the usefulness of chemical compounds in the treatment and/or prevention of disease in man and other animals depends upon the chemotherapeutic ratio of such compounds, that is, the quotient of the toxic dose to the dose effective for the required purpose. As this ratio increases, the safety and consequently the usefulness of the compound increase.
Most chemical compounds which are used in the treatment or prevention of disease (hereinafter referred to for convenience as "drugs") undergo a wide range of chemical transformations in the body of the host. This is due to the action of the enzymes of the organs and tissues of the host and to the activities of extraneous biological agents present in the body of the host, principally microorganisms residing in the intestinal tract.
Numerous examples can be given of drugs which themselves have low toxicity, but which are converted or metabolized by the above mentioned chemical transformations, either partially or in some cases completely, into products that demonstrate far greater chronic and acute toxic properties than the drug itself. The metabolism or transformation which occurs may or may not affect the therapeutic or prophylactic activity of the active compound. In any case, however, the transformation can reduce the chemotherapeutic ratio of the compound and, therefore, its value and scope of use. As an illustration of this, reference may be made to such antischistosomal drugs as hycanthone which, although demonstrating significant antischistosomal activity, are also mutagenic and carcinogenic apparently because of some sort of chemical transformation in the host body. As a consequence, these drugs can only find limited, if any, use since the potential benefits of using the drug need to be weighed against possible long-range risks.